Circulating Serum MicroRNA-130a as a Novel Putative Marker of Extramedullary Myeloma

Poor outcome of extramedullary disease in multiple myeloma patients and lack of outcome predictors prompt continued search for new markers of the disease. In this report, we show circulating microRNA distinguishing multiple myeloma patients with extramedullary disease from myeloma patients without such manifestation and from healthy donors. MicroRNA-130a was identified by TaqMan Low Density Arrays and verified by quantitative PCR on 144 serum samples (59 multiple myeloma, 55 myeloma with extramedullary disease, 30 healthy donors) in test and validation cohorts as being down-regulated in myeloma patients with extramedullary disease. Circulating microRNA-130a distinguished myeloma patients with extramedullary disease from healthy donors with specificity of 90.0% and sensitivity of 77.1%, patients with extramedullary disease from newly diagnosed multiple myeloma patients with specificity of 77.1% and sensitivity of 34.3% in the test cohort and with specificity of 91.7% and sensitivity of 30.0% in the validation cohort of patients. Circulating microRNA-130a in patients with extramedullary myeloma was associated with bone marrow plasma cells infiltration. Further, microRNA-130a was decreased in bone marrow plasma cells obtained from patients with extramedullary myeloma in comparison to bone marrow plasma cells of myeloma patients without such manifestation, but it was increased in tumor site plasma cells of patients with extramedullary disease compared to bone marrow plasma cells of such patients (p<0.0001). Together, our data suggest connection between lower level of microRNA-130a and extramedullary disease and prompt further work to evaluate this miRNA as a marker of extramedullary disease in multiple myeloma.     

Serum protein N-glycosylation changes in multiple myeloma

BackgroundMultiple myeloma is characterized by clonal proliferation of malignant plasma cells in the bone marrow that produce monoclonal immunoglobulins. N-glycosylation changes of these monoclonal immunoglobulins have been reported in multiple myeloma, but previous studies only detected limited serum N-glycan features.MethodsHere, a more detailed study of the human serum N-glycome of 91 multiple myeloma patients and 51 controls was performed. We additionally analyzed sequential samples from patients (n = 7) which were obtained at different time points during disease development as well as 16 paired blood serum and bone marrow plasma samples. N-glycans were enzymatically released and measured by mass spectrometry after linkage specific derivatization of sialic acids.ResultsA decrease in both α2,3- and α2,6-sialylation, galactosylation and an increase in fucosylation within complex-type N-glycans were found in multiple myeloma patients compared to controls, as well as a decrease in difucosylation of diantennary glycans. The observed glycosylation changes were present in all ISS stages, including the “low-risk” ISS I. In individual patients, difucosylation of diantennary glycans decreased with development of the disease. Protein N-glycosylation features from blood and bone marrow showed strong correlation. Moreover, associations of monoclonal immunoglobulin (M-protein) and albumin levels with glycan traits were discovered in multiple myeloma patients.Conclusions & general significanceIn conclusion, serum protein N-glycosylation analysis could successfully distinguish multiple myeloma from healthy controls. Further studies are needed to assess the potential roles of glycan trait changes and the associations of glycans with clinical parameters in multiple myeloma early detection and prognosis.     

Immunoglobulin crystal-storing histiocytosis in a pleural effusion from a woman with IgA kapa multiple myeloma: a case report

BACKGROUND: Crystal-storing histiocytosis (CSH) is a rare disorder occurring in patients with lymphoproliferative diseases, predominantly multiple myeloma and low grade B-cell lymphoma. This report presents the first case of CSH diagnosed on pleural fluid from a patient with multiple myeloma (MM). CASE: A 79-year-old women with IgA kappa MM underwent thoracocenthesis and thoracic drainage because of a pleural effusion. Cytologic and immunocytochemical examination of pleural fluid revealed abundant histiocytic, CD68-positive cells with prominent intracytoplasmic, needlelike, crystalloid inclusions showing strong immunopositivity for IgA heavy and kappa light chains. Identical crystals were observed on an extracellular background. No myeloma infiltration was detected. Two weeks later, examination of new pleural fluid from the patient showed a similar cytologic picture, but, in addition, isolated plasma cell features were identified. They were too few for a meaningful determination of clonality. The patient died I month after the CSH diagnosis. CONCLUSION: This case illustrates the value of cytologic examination of serous fluids from patients with plasma cell dyscrasias, not only to evaluate possible infectious or neoplastic causes but also to diagnose CSH.     

Genomic instability in Multiple Myeloma-relevance for Clinical Outcome and Efficacy of Therapy

Genomic instability is a driving force in the natural history of blood cancers including multiple myeloma,an incurable neoplasm of immunoglobulin producing plasma cells that reside in the hematopoietic bone marrow. Long recognized manifestations of genomic instability in myeloma at the cytogenetic level include abnormal chromosome numbers (aneuploidy) caused by trisomy of odd-numbered chromosomes; recurrent oncogene-activating chromosomal translocations that involve immunoglobulin loci; and large-scale amplifications, inversions, and insertions / deletions (indels). Catastrophic genetic rearrangements that either shatter and illegitimately reassemble a single chromosome (chromotripsis) or lead to disordered segmental rearrangements of multiple chromosomes (chromoplexy) also occur. Genomic instability at the nucleotide level results in base substitution mutations and small indels that affect both the coding and non-coding genome. Distinctive signatures of somatic mutations that can be attributed to defects in DNA repair pathways, the DNA damage response or aberrant activity of mutator genes including members of the APOBEC family have been identified. Here we review recent findings on genomic stability control in myeloma that are not only relevant for myeloma development and progression, but also underpin disease relapse and acquisition of drug resistance in patients with myeloma.     

Assessing the efficiency of free light chain assay in monitoring patients with multiple myeloma before and after autologous stem cell transplantation along with serum protein electrophoresis and serum protein immunofixation

Monoclonal gammopathies are a group of disorders, referred to as paraproteinaemias, dysproteinaemias or immunoglobulinopathies, associated with monoclonal proliferation of plasma cells. Monoclonal immunoglobulin secreted by these cells is an indicator of clonal proliferation. The aim of this study is to analyze the efficiency of three methods: serum protein electrophoresis (SPE), serum protein immunofixation (IFE) and FLC (free light chain) assay for the diagnosis and monitoring of the tumor burden in multiple myeloma. In this study we have presented the dynamic evolution of 7 patients with intact immunoglobulin multiple myeloma (IIMM) (2 IgG, kapa; 3 IgG, lambda; 1 IgA, kappa; 1 IgA, lambda) and 2 patients with light chain multiple myeloma before and after autologous peripheral blood stem cell transplantation (PBSCT). All 7 patients fulfilled the four criteria for the diagnosis of IIMM: bone marrow plasma cells exceeding 20%, lytic bone lesions, identification and quantification of M protein by scanning densitometry of electrophoresis gels, IFE (immunofixation protein electrophoresis) confirmed and typed the M protein. All patients had been given cytotoxic chemotherapy (VAD or VELCADE) before autologous (PBSCT). In two of the patients with IIMM both SPE and kappa/lambda ratio fell towards normal range after autologous PBSC and both reported a relapse of the disease after 23 months and 19 months respectively. SPE could not normalize after chemotherapy and transplantation in three patients with IIMM, the kappa/lambda ratio being the only marker used to monitor the tumor kill. In one patient the kappa/lambda ratio could not normalize even after PBSCT still indicating the presence of plasma cell disorder at the time when IFE was still negative. 16 months after PBSCT both SPE and FLC indicated a relapse of the disease. Classical SPE failed to demonstrate the presence of M-protein in light chain multiple myeloma, the diagnosis being established by using IFE and the FLC assay. Because IFE is a qualitative method and its interpretation may be sometimes subjective, FLC was the only method used to follow the disease course. The measurement of kappa/lambda ratio proved to be more sensitive than SPE, IFE and the levels of free light chains kappa or lambda individually indicating whether the treatment is effective or not.     

Phenotypic detection of clonotypic B cells in multiple myeloma by specific immunoglobulin ligands reveals their rarity in multiple myeloma

In multiple myeloma, circulating "clonotypic" B cells, that express the immunoglobulin rearrangement of the malignant plasma cell clone, can be indirectly detected by PCR. Their role as potential "feeder" cells for the malignant plasma cell pool remains controversial. Here we established for the first time an approach that allows direct tracking of such clonotypic cells by labeling with patient-specific immunoglobulin ligands in 15 patients with myeloma. Fifty percent of patients showed evidence of clonotypic B cells in blood or bone marrow by PCR. Epitope-mimicking peptides from random libraries were selected on each patient's individual immunoglobulin and used as ligands to trace cells expressing the idiotypic immunoglobulin on their surface. We established a flow cytometry and immunofluorescence protocol to track clonotypic B cells and validated it in two independent monoclonal B cell systems. Using this method, we found clonotypic B cells in only one out of 15 myeloma patients. In view of the assay's validated sensitivity level of 10(-3), this surprising data suggests that the abundance of such cells has been vastly overestimated in the past and that they apparently represent a very rare population in myeloma. Our novel tracing approach may open perspectives to isolate and analyze clonotypic B cells and determine their role in myeloma pathobiology.     

Monoclonal gammopathies of undetermined significance

The term 'monoclonal gammopathy of undetermined significance' denotes the presence of a monoclonal protein in patients without evidence of multiple myeloma, macroglobulinemia, amyloidosis or related plasma cell proliferative disorders. The disorder has been found in approximately 3% of persons older than 70 years and in approximately 1% of persons older than 50 years. A population-based study included 1384 patients from south-eastern Minnesota who had the disorder diagnosed at the Mayo Clinic from 1960 through 1994. Risk of progression was about 1% per year, but patients were at risk of progression even after 25 years or more of stable monoclonal gammopathy of undetermined significance. The risk for development of multiple myeloma was increased 25-fold; the risk of macroglobulinemia, 46-fold; and the risk of primary amyloidosis, 8.4-fold. Concentration and type of monoclonal protein were the only independent predictors of progression. The presence of a urine monoclonal protein and the reduction of one or more uninvolved immunoglobulins were not risk factors for progression. Monoclonal gammopathy of undetermined significance may be associated with various disorders, including lymphoproliferative diseases, leukemia, von Willebrand disease, connective tissue diseases and neurologic disorders.     

CD56、CD117表达水平与来那度胺治疗多发性骨髓瘤疗效的相关性分析

目的:探讨CD56、CD117的表达水平与来那度胺治疗多发性骨髓瘤疗效的相关性,为预测来那度胺治疗多发性骨髓瘤的疗效提供参考依据。方法:将我院2016年12月至2019年3月收治的多发性骨髓瘤患者64例,均给予来那度胺联合小剂量地塞米松治疗,所有患者根据疗效分为完全缓解(CR)、非常好的部分缓解(VGPR)、部分缓解(PR)、疾病稳定(SD)、疾病进展(PD),并且采用门诊、电话、住院等随访方式定期随访。采用流式细胞仪测定所有患者入院治疗前一天的CD56、CD117的表达水平,分析CD56、CD117表达与患者病理特征以及来那度胺疗效的相关性。结果:CD56、CD117的表达水平与多发性骨髓瘤患者的轻链分型、M蛋白分型、临床分型显著相关,与性别无关。来那度胺治疗多发性骨髓瘤的64例患者中,有效例数53例,总有效率为83%;其有效组患者中,CD56、CD117的阳性率分别为56.6%、35.8%,显著高于无效组患者(18.2%、9.1%)(P<0.05)。结论:多发性骨髓瘤患者CD56、CD117均呈现高表达的状态,其表达与患者的临床分期、M蛋白类型、轻链重链类型及来那度胺治疗的疗效有显著相关性。     

Phenotypic and genotypic alterations characterize patients bearing plasma cell dyscrasias with a high M-component

As at present only a long-term follow-up can fully determine whether monoclonal gammapathies of undetermined significance (MGUS) will evolve into multiple myeloma (MM), this study attempted to identify other variables connected with the amount of monoclonal component (MC), generally considered as the most reliable marker of malignant evolution. Thirty-four MGUS subjects showing a high MC (> or = 15.0 g/l) but without clinical evidence of MM (MGUS group b), were characterized for their phenotypic and genotypic profile by comparing them either with 40 MM patients or with 24 subjects affected by a benign form of monoclonal gammapathy (MGUS group a) according to the standard criteria. In addition to the usual laboratory markers, the levels of expression of a panel of CD membrane subsets were measured on B and T lymphocytes. Also, the serum level of the p53 mutant protein and the structural alterations of the c-myc oncogene were evaluated. The results show that for MGUS group b patients, an increased M-protein was accompanied by significantly increased levels of peripheral blood CD3+ T cells and oncogenetic aberrations in c-myc. Since a high serum MC level seems to indicate a greater likelihood of malignant transformation for MGUS patients, these findings suggest that this relationship may be a result of the concomitant alterations observed at a phenotypic and genotypic level. Such alterations may be potentially useful as surrogate markers for the transition of benign to malignant (MM) plasma cell dyscrasia.     

Interleukin-6 is the central tumor growth factor in vitro and in vivo in multiple myeloma

When bone-marrow cells from patients with multiple myeloma (MM) were seeded in short-term cultures, a spontaneous proliferation of the myeloma cells occurred for most of the patients with active disease and proliferating myeloma cells in vivo. In all cases, this spontaneous proliferation was inhibited by anti-IL-6 monoclonal antibodies (mabs). Moreover, myeloma cell lines, completely dependent upon exogenous IL-6 for their growth, could be reproducibly established by initially stimulating the myeloma cells with both IL-6 and GM-CSF. These results demonstrate that IL-6 is a major paracrine myeloma-cell growth factor in vitro. High serum IL-6 levels were observed in MM patients with active disease, especially patients with terminal disease. High IL-6 mRNA levels were found in bone-marrow cells of MM patients, mainly in myeloid and monocytic cells, in vivo. The myeloma cells did not express IL-6 mRNA. Injection of anti-IL-6 mabs to MM patients with terminal disease and extramedullary proliferation, completely blocked the myeloma-cell proliferation in vivo and completely inhibited the serum IL-6 bioactivity and the serum CRP levels. One patient with plasma cell leukemia and hypercalcemia was treated for two months with anti-IL-6 mabs and maintain in remission for 2 months without major side effects. Interestingly, the serum calcium levels also decreased in these patients. All these results show that IL-6 is the main cytokine responsible not only for the myeloma-cell proliferation in vivo, but presumably also for the large bone resorption processes observed in human MM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Breast myeloma: a report of 3 cases with fine needle aspiration cytologic findings

BACKGROUND: Multiple myeloma of the breast is very rare, and the fine needle aspiration (FNA) findings have not been reported before. CASES: Two cases of multiple myeloma presented with bilateral breast nodules during treatment with chemotherapy. One case of multiple myeloma presented initially with a left breast mass. FNA smears of all 3 cases revealed numerous plasma cells, plasmablasts and multinucleated giant plasma cells. The smears were diagnosed as plasma cell tumors. Serum immunoelectrophoresis revealed IgG myeloma in 2 cases and IgA myeloma in 1. Marrow aspirates revealed > 30% plasma cells. Two patients died, and 1 was alive at this writing. CONCLUSION: The aspiration cytology findings of myeloma can be confuse, with primary and secondary tumors of the breast. The previous clinical history and ancillary studies, such as bone marrow study and serum immunoelectrophoresis, are essential to the correct diagnosis.     

Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology

U. Handa, S. Chhabra and H. Mohan
Plasma cell tumours: cytomorphological features in a series of 12 cases diagnosed on fine needle aspiration cytology Objective: Plasma cell tumours represent autonomous proliferation of plasma cells and can manifest as multiple myeloma, monoclonal gammopathy of undetermined significance, variants of plasma cell myeloma or plasmacytoma. Methods: We report 12 cases of plasma cell tumours, which were initially diagnosed as plasmacytoma on fine needle aspiration cytology (FNAC). The patients were further subjected to bone marrow examination, serum electrophoresis, urine examination for Bence–Jones proteins, and x‐ray examination of the skeleton. Results: The cytological smears from all cases were cellular and showed numerous plasma cells in varying degrees of maturity. Subsequent to investigations, five cases were labelled as multiple myeloma with secondary extramedullary plasmacytoma, three as solitary bone plasmacytoma and two as primary extramedullary plasmacytoma. In the remaining two cases, bone marrow and urine examination findings were not available, so a conclusive diagnosis of multiple myeloma or solitary plasmacytoma could not be made. Conclusion: The study highlights the role of FNAC in the diagnosis of plasma cell tumours. Subsequent work‐up and follow‐up of these patients is important to rule out the presence of multiple myeloma.     

Molecular Basis of Differential Sensitivity of Myeloma Cells to Clinically Relevant Bolus Treatment with Bortezomib

The proteasome inhibitor bortezomib (Velcade) is prescribed for the treatment of multiple myeloma. Clinically achievable concentrations of bortezomib cause less than 85% inhibition of the chymotrypsin-like activity of the proteasome, but little attention has been paid as to whether in vitro studies are representative of this level of inhibition. Patients receive bortezomib as an intravenous or subcutaneous bolus injection, resulting in maximum proteasome inhibition within one hour followed by a gradual recovery of activity. In contrast, most in vitro studies use continuous treatment so that activity never recovers. Replacing continuous treatment with 1 h-pulse treatment increases differences in sensitivity in a panel of 7 multiple myeloma cell lines from 5.3-fold to 18-fold, and reveals that the more sensitive cell lines undergo apoptosis at faster rates. Clinically achievable inhibition of active sites was sufficient to induce cytotoxicity only in one cell line. At concentrations of bortezomib that produced similar inhibition of peptidase activities a different extent of inhibition of protein degradation was observed, providing an explanation for the differential sensitivity. The amount of protein degraded per number of active proteasomes correlated with sensitivity to bortezomib. Thus, (i) in vitro studies of proteasome inhibitors should be conducted at pharmacologically achievable concentrations and duration of treatment; (ii) a similar level of inhibition of active sites results in a different extent of inhibition of protein breakdown in different cell lines, and hence a difference in sensitivity.     

Inadequate erythropoietin production (epo) in patients with multiple myeloma

Anaemia is the most common haematological complication in patients with malignant diseases. It is found in 60%-90% of cases with multiple myeloma. The pathogenesis of this hypoproliferative, normochromic, normocytic anaemia is complex. Results from clinical studies which evaluate the efficacy of recombinant human erythropoietin (rHuEpo) refer to the possibility that patients with multiple myeloma independently of renal function could have Epo deficiency. Based on this finding, the aim of the study was to evaluate the erythropoietin production in patients with multiple myeloma in order to define clinical conditions of Epo deficiency and thereby enable rational use of this expensive drug. 42 patients with multiple myeloma were examined. The control group consisted of 25 patients with iron deficiency anaemia. 14 healthy volunteers represented the so-called "normal" control. The adequacy of Epo production was estimated from the graphic representation of the linear regression between Epo and haemoglobin (Hb) in the control group, as well as from O/PEpo ratio as a measure of the degree of adequacy of Epo production (O -- observed Epo value, P -- predicted Epo value from the regression equation of the control group). The erythropoietic activity was estimated from the graphic representation of the linear regression between soluble transferin receptors (sTfR) and Hb in the control group, as well as from O/PsTfR ratio, as a measure of the degree of adequacy of erythropoietic activity (O -- observed sTfR value, P -- predicted sTfR value from the regression equation of the control group). Significant inverse correlation between Epo and Hb was found in patients with multiple myeloma but preserved renal function, which was not the case in patients with renal insufficiency. 43% of patients without renal insufficiency and 85% of patients with renal insufficiency had inadequate Epo response to anaemia. In both patient groups (with and without renal insufficiency) instead of the expected inverse relationship between Hb and sTfR as in the control group, a positive correlation was found. 76% of patients had inadequate sTfR response to anaemia. There is a positive correlation between O/PEpo and O/PsTfR which is in favour of Epo driven erythropoiesis. O/PEpo and O/PsTfR in patients with multiple myeloma are significantly lower in comparison to the control group, which also points to the inadequacy of erythropoietin production, respectively erythropoietic activity. In conclusion, the results from this study show unambiguously that anaemia in patients with multiple myeloma appears because of decreased erythropoiesis as a consequence of bone marrow infiltration with malignant plasma cells as well as inadequate Epo production. Most probably, there are two forms of inadequate Epo production: one because of the renal insufficiency and the other that found in patients with anaemia of chronic diseases the mechanism of which is not clear.     

Paraproteins associated with low plasma sodium levels

The mechanism of the maintenance of low plasma sodium levels seen in certain multiple myeloma cases has been attributed to the cationic nature of pathological immunoglobulins (paraproteins). This hypothesis was tested with equilibrium dialysis and polyacrylamide gel electrophoresis techniques. Citrated plasma samples and affinity chromatography purified paraproteins of three multiple myeloma patients with abnormally low plasma sodium levels were dialysed against 140 mmol/L NaCl solution at pH 7.4 for 24 hours. The electrophoresis of paraproteins was conducted under non-denaturing conditions. Low plasma sodium concentrations observed under the dialysis of the patients' plasma samples were in good agreement with earlier reports. However, the isolated paraproteins did not show any sodium exclusion during the dialysis experiment. The electrophoretic mobility of the paraproteins at pH 7.4 indicated that the isoelectric point of these molecules was below 7.4, so they cannot behave as cations at the pH of the blood. From these data it appears that the maintenance of low plasma sodium levels in certain IgG type myeloma cases cannot be explained by the previously postulated cationic nature of the paraproteins.     

Interleukin-6 and the network of several cytokines in multiple myeloma: an overview of clinical and experimental data.

Study of the network of cytokines has helped identify cell growth factors in multiple myeloma. Plasma cells themselves may produce autocrine interleukin 6 (IL-6) while IL-6 production by bone marrow stromal cells may operate a paracrine mechanism. Involvement of IL-6 in multiple myeloma is indicated by its ability to induce the differentiation of myeloma plasmablasts into mature malignant plasma cells. Differential diagnosis between multiple myeloma and monoclonal gammopathies of undetermined significance (MGUS) is generally based on clinical and laboratory parameters. Nevertheless, evaluation of the serum level of IL-6, C reactive protein, soluble IL-6 receptor, soluble IL-2 receptor together with the activity exerted by IL-3 and IL-4 on some cellular subsets constitutes an additional element in the differential diagnosis of border-line cases. Serum levels of IL-6, soluble IL-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R) and the expression of membrane-bound IL-2 receptors, both on bone marrow plasma cells and on peripheral blood mononuclear cells are correlated with disease activity and disease stage. In addition, IL-6 and sIL-6R serum levels correlate with the duration of survival, as high values at the time of diagnosis correlate with short duration of survival.     

Whole body MR in patients with multiple myeloma

BackgroundMultiple myeloma is a cancer of plasma cells which leads to bone marrow infiltration.AimWhole-body MR is the most sensitive imaging method available to detect multiple myeloma lesions.Material and MethodsMR scans were performed in 100 patients with multiple myeloma who were receiving treatment in the Haematology Clinic in Poznań in the years 2005–2006. Whole-body MR scans were performed with general coil 1.0 T in STIR sequences and T1 sequences, in coronal and sagittal planes with scanning area covering the head, neck, trunk and the limbs (FOV for specific regions was 36–48 cm). The bone lesions were classified as focal (monofocal/multifocal lesions), in-filtrative, mixed and “salt and pepper” type. Depending on the size of the lesions the patients were included in one of three groups according to Salmon-Durie Plus classification.ResultsFour main types of multiple myeloma were distinguished based on MR scans: focal (48 patients; monofocal in 10 patients), infiltrative (17 patients), mixed type (19 patients) and “salt and pepper” type (4 patients). The remaining 12 patients had no multiple myeloma lesions in the bone marrow. Additionally, in 18% of patients a soft tissue mass could be observed. According to Salmon-Durie Plus categorisation 27 subjects were classified as having stage I, 16 patients stage and 57 patients stage III disease. In 12% of patients MR data changed the disease staging.ConclusionsWB MR is a sensitive and effective diagnostic method with an important impact on staging and further treatment of multiple myeloma.     

Identification and evaluation of a panel of serum biomarkers for predicting response to thalidomide in multiple myeloma patients

Evaluation of: Rajpal R, Dowling P, Meiller J et al. A novel panel of protein biomarkers for predicting response to thalidomide-based therapy in newly diagnosed multiple myeloma patients. Proteomics 11(8), 1391-1402 (2011). Predicting response to thalidomide-based therapy remains a challenging task faced by clinicians in the treatment of multiple myeloma. The pioneering work reported by Rajpal et al. moves one step further towards solving this challenge. They developed a proteomics-based approach that combines immunodepletion, 2D-difference gel electrophoresis analysis and mass spectrometry to search for serum proteins with expressions that show significant correlations to thalidomide treatment. This integrated approach allowed them to identify a panel of protein biomarkers. By using ELISA-based validation and strict statistical analysis, the authors have achieved an overall 84.0% predictive accuracy, with associated sensitivity and specificity values of 81.8 and 86.2%, respectively. Their methods and significant findings are reviewed within this article. This panel of biomarkers may not only guide initial therapy, but can also provide direct implications for personalized medicine in multiple myeloma patients.     

Quantitation of monoclonal plasma cells in bone marrow biopsies in plasma cell dyscrasia.

Direct measurement of monoclonal plasma cell mass in bone marrow biopsies may be a useful parameter to establish in plasma cell dyscrasia. In this study monoclonal plasma cells/mm in light chain immunoglobulin immunostained archival bone marrow sections from 22 patients in whom a diagnosis of multiple myeloma (MM) had been excluded but who had monoclonal proteins were counted by two observers at light microscopic level. There was good correlation between the counts of the two observers. The levels of monoclonal plasma cells/mm in biopsies were not related to the % counts in the aspirates taken at the same time as the biopsies. Three of seven patients with biopsy levels in excess of the polyclonal levels in patients without plasma cell dyscrasia developed progressive MM within the observation time. Monoclonal plasma cell levels/mm of bone marrow biopsies can be measured and they provide a useful parameter for the assessment of patients with low volume plasma cell dyscrasia.